Anti-inflammatory and antinociceptive activities of azadirachtin in mice.
2014
Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory
and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the
major bioactive compound found in the extracts, have been poorly investigated in animal models.
In the present study, we investigated the effects induced by azadirachtin in experimental models
of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth
induced by subcutaneous cotton pellet implantation were used to investigate the
anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests
were employed to evaluate the antinociceptive activity. To explore putative mechanisms of
action, the level of tumor necrosis factor- α in inflammatory tissue was measured and the
effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os
(p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema
induced by carrageenan. However, the concomitant increase of the paw concentration of tumor
necrosis factor- α induced by this inflammatory stimulus was not reduced by azadirachtin.
In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and
120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by
the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited
the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced
by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was
attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a
nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the
activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also
in models of acute and chronic inflammation. Finally, multiple mechanisms, including the
inhibition of the production of inflammatory mediators and activation of endogenous opioid
pathways, may mediate azadirachtin activities in experimental models of inflammation and
pain.
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